Intermediate metabolites of the pyrimidine metabolism pathway extend the lifespan of C. elegans through regulating reproductive signals
Intermediate metabolites of the pyrimidine metabolism pathway extend the lifespan of C. elegans through regulating reproductive signals
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嘧啶代谢途径的中间代谢产物通过调节生殖信号延长线虫的寿命
DOI：
10.18632/aging.102033
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发表时间：
2019-06
期刊：
影响因子：
5.2
通讯作者：
Zhou Qinghua
中科院分区：
文献类型：
--
作者：
Wan Qin Li;Meng Xiao;Fu Xiaodie;Chen Bohui;Yang Jing;Yang Hengwen;Zhou Qinghua
嘧啶代谢途径具有重要的生物学功能，它不仅维持适当的嘧啶库，而且产生具有生物活性的中间代谢产物。在以前的研究中，我们发现嘧啶代谢途径与衰老调节有关。然而，嘧啶代谢途径调节衰老的分子机制仍不清楚。在这里，我们研究了嘧啶中间体对秀丽隐杆线虫（C。elegans）。实验结果表明，添加某些嘧啶中间体可以延长C.优雅的。此外，参与嘧啶代谢的必需酶的RNAi敲低也可以显著影响寿命。我们进一步研究了一种代表性的中间代谢物胸腺嘧啶延长蠕虫寿命的分子机制，发现胸腺嘧啶诱导的寿命需要核受体α-12和NHR-49以及转录因子β-16/FOXO。进一步的通路分析表明，胸腺嘧啶的长寿效应依赖于抑制生殖信号。此外，我们发现其他嘧啶中间体以类似于胸腺嘧啶的方式发挥作用，以延长C。优美的综上所述，我们的研究结果表明，嘧啶中间体通过抑制生殖信号并随后诱导C.优美的
The pyrimidine metabolism pathway has important biological functions; it not only maintains appropriate pyrimidine pools but also produces bioactive intermediate metabolites. In a previous study, we identified that the pyrimidine metabolism pathway is associated with aging regulation. However, the molecular mechanism by which the pyrimidine metabolism pathway regulates aging remains unclear. Here, we investigated the longevity effect of pyrimidine intermediates on Caenorhabditis elegans (C. elegans). Our results demonstrated that the supplementation of some pyrimidine intermediates could extend the lifespan of C. elegans. In addition, the RNAi knockdown of essential enzymes involved in pyrimidine metabolism could also significantly affect lifespan. We further investigated the molecular mechanism by which a representative intermediate metabolite, thymine, extends the lifespan of worms and found that thymine-induced longevity required the nuclear receptors DAF-12 and NHR-49, and the transcription factor DAF-16/FOXO. Further pathway analysis revealed that the longevity effect of thymine depended on the inhibition of reproductive signals. Additionally, we found that other pyrimidine intermediates functioned in a manner similar to thymine to prolong lifespan in C. elegans. Taken together, our results revealed that pyrimidine intermediates increased lifespan by inhibiting reproductive signals and subsequently inducing the function of DAF-12, NHR-49 and DAF-16 in C. elegans.
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影响因子：
64.5
作者：
López-Otín C;Blasco MA;Partridge L;Serrano M;Kroemer G
通讯作者：
Kroemer G
影响因子：
64.5
作者：
Scott TA;Quintaneiro LM;Norvaisas P;Lui PP;Wilson MP;Leung KY;Herrera-Dominguez L;Sudiwala S;Pessia A;Clayton PT;Bryson K;Velagapudi V;Mills PB;Typas A;Greene NDE;Cabreiro F
通讯作者：
Cabreiro F
影响因子：
7.8
作者：
McCormick M;Chen K;Ramaswamy P;Kenyon C
通讯作者：
Kenyon C
影响因子：
64.5
作者：
Fontana L;Partridge L
通讯作者：
Partridge L
DOI：
10.1007/978-3-662-49771-5_19
发表时间：
2016
期刊：
--
影响因子：
--
作者：
J. Häberle;V. Rubio
通讯作者：
J. Häberle;V. Rubio